Several researchers have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) in various neurodegenerative disorders, including demyelinating diseases. However, this effect was generally observed only locally, in the surrounding area where the MSCs were transplanted. Moreover, current treatments modifying the pathological mechanisms are capable of ameliorating the disease symptoms, but are frequently insufficient to repress the progressive loss of myelin and promote functional recovery. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles of chronic demyelinated mice. In this manner, the first section of this work shows that the cells may secrete soluble trophic factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). The results indicated an enhanced recruitment of oligodendrocyte progenitor cells (OPCs) within the corpus callosum (CC) over time, which was correlated with an increase in myelin content. Electrophysiological studies, together with electron microscopy analysis corroborated that the newly-formed myelin was functional. Whereas the number of astrocytes seemed to be unaffected, an enhancement in the proliferation of neural stem progenitor cells (NSPCs) was detected in the SVZ, possibly due to their contact with the tropic factors released in the CSF. Hence, the findings of this study revealed that MSCs intraventricular-injection is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the secreted factors and therefore promoting oligodendrogenesis and functional remyelination. Similarly, the second part of this work reveals that the fibroblast growth factor 8 (FGF8), a key molecular signal for early embryonic development of the central nervous system, was capable of activating mouse post-natal OPCs in vitro. The results demonstrated that FGF8 is a novel factor to induce OPCs activation, migration, and increase their proliferation, without impairing their differentiation. In conclusion, both strategies were proven as very interesting alternative treatments for demyelinating diseases.